Although the cure rate of childhood ALL is among the highest of any cancers, there is still significant room for improvement both because some children still succumb to their disease and because others may obtain more treatment than is necessary for cure. Almost all children enter remission following initial therapy, but may patients harbor residual disease below the level that can be detected by conventional measurements. There is a growing body of evidence that presence of this minimal residual disease (MRD) may be an adverse prognostic factor. This project is designed to study children with ALL who are enrolled on front-line clinical trials of the Pediatric Oncology Group for newly diagnosed leukemia. The current study will employ a highly sensitive four color flow cytometric technique to study MRD and will answer the following questions: 1) What is the frequency with which children with ALL have phenotypically abnormal cells in the bone marrow or blood following induction therapy, or at the end of consolidation therapy, and what is the quantitative residual disease burden in such patients? 2) How dose the presence of MRD correlate with traditional risk factors? 3) Do patients with MRD have an increased risk of relapse and what quantitative level of positivity is optimal for distinguishing between higher and lower risk patients? 4) Do children with ALL who harbor MRD and receive more intensive therapy have a better outcome than those who do not receive this extra therapy? In preliminary experiments, he has found that he can detect residual leukemic blasts in the blood or marrow of some patients at the end of induction therapy. The range of postivity he has detected so far is from 0.33 percent to as low as .0054 percent of total cells. The studies described here will be closely integrated with other studies proposed in a companion grant as part of this IRPG. These other proposed studies will use molecular techniques to detect residual disease on the same samples tested here. Another goal of their study therefore is to compare flow and molecular technologies and determine the most sensitive, most predictive, and most cost-effective technical approach for the detection of clinically significant residual leukemic burden.